CN109142657A - A kind of detection analysis instrument - Google Patents
A kind of detection analysis instrument Download PDFInfo
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- CN109142657A CN109142657A CN201710508203.5A CN201710508203A CN109142657A CN 109142657 A CN109142657 A CN 109142657A CN 201710508203 A CN201710508203 A CN 201710508203A CN 109142657 A CN109142657 A CN 109142657A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
Abstract
This application discloses a kind of detection analysis instruments comprising the first sample input/output element, the second sample input/output element, sample bin, shaking platform, oscillator, data collection system and data display equipment；Wherein, first sample input/output element and second sample input/output element are connected to the sample bin respectively；The shaking platform is located in the sample bin；The oscillator is located at outside the sample bin, and the shaking platform is connect with the oscillator；The data collection system is located at outside the sample bin, and connect with the shaking platform；The data display equipment is connect with the data collection system.
Description
Technical field
This application involves a kind of detection analysis instruments, in particular to a kind of to be used for multi-modal, dynamic biological toxicity real-time quantitative
The analyzer of detection.
Background technique
Currently, microelectromechanical systems is a kind of technology that comparison is popular, which is built upon micro-/ nano technical foundation
On front subject.By being designed, processing, manufacturing and controlling to micro/nano material, can by mechanical construction, optical system,
Driving part, electric-control system, digital processing system are integrated into an integral unit.This microelectromechanical systems can not only adopt
Collection, processing and transmission information or instruction, additionally it is possible to according to acquired information independence or according to external command take action.It
Microelectric technique and the manufacturing process that micro-processing technology combines, can use its manufacture out it is various have excellent performance, valence
Sensor, actuator, driver and the micro-system that lattice are cheap, are miniaturized.
It is different from traditional machinery, the machinery in microelectromechanical systems represents all effects with functions such as energy conversions
Answer, including power, heat, sound, light, magnetic or even chemical-biological etc., thus microelectromechanical systems be related to machinery, electronics, chemistry,
The subjects such as physics, biology, material.Under micro-meter scale, micro mechanical structure still follows traditional Laws of Mechanics, but with ruler
Very little diminution, quality, thermal capacitance of micro mechanical device etc. reduce, and electrostatic force, resonance frequency, specific surface area etc. increase.On the one hand, sharp
The performances such as response time, sensitivity and the bandwidth of operation of micro mechanical device can be improved with these dimensional effects, on the other hand, this
A little changing rules make micromechanics be easy to be interfered by temperature, humidity etc..
In addition, as bio-medical material and product have been widely used in clinical medicine, so the biology of evaluation material
Toxicity is most important.
On the basis of common cytotoxicity assay is built upon drug to cytosis influence both at home and abroad at present, lead to
Cross cell marker recognition, quantity statistics, time point type analysis method evaluate cytotoxicity, such as: mtt assay, LDH method etc.,
But chemical staining agent used in these measurement methods or fluorescence indicator etc. will cause the permanent injury of cell, and wink
When time point toxicity measurement result also can not meet the requirement that interim investigation is carried out to dealed with medicine went, to cannot make
To entire intoxication process carry out in real time, it is accurate, observe and detect to continuous effective, in addition, these methods are not really to anticipate
Quantitative detection in justice can only be half-quantitative detection.So, it may be considered that resonance micro-cantilever sensor-based system is applied to biology
The context of detection of toxicity.
Summary of the invention
The shortcomings that in order to overcome traditional biological detection method of toxicity: 1) quantity statistics, half-quantitative detection；2) chemical stain meeting
Possible permanent damage is caused to cell；3) time point type analysis method is taken.To realize continuous, long-time, real-time, quantitative, multimode
The purpose of dynamic monitoring, the application have developed a kind of multi-modal, dynamic biological toxicity Real_time quantitative detection analyzer.
Therefore, this application provides a kind of detection analysis instruments comprising the first sample input/output element, the second sample
Input/output element, sample bin, shaking platform, oscillator, data collection system and data display equipment；Wherein, first sample
Product input/output element and second sample input/output element are connected to the sample bin respectively；The shaking platform position
In in the sample bin；The oscillator is located at outside the sample bin, and the shaking platform is connect with the oscillator；Institute
It states data collection system to be located at outside the sample bin, and is connect with the shaking platform；The data display equipment and the data
Acquisition system connection.
Wherein, according to the actual situation, sample bin can keep constant temperature.
In a specific embodiment, the shaking platform is made of pressure sensitive or vibration quartz material.
In a specific embodiment, the shaking platform is the structure with wafer type, may be to have side
The structure of piece type.
In a specific embodiment, the edge of the shaking platform is fixedly connected with elastic element, the elasticity member
Part is connect with external voltage.Wherein, elastic element can be selected from gold plaque and/or platinum piece.And the elastic element is by silica gel
Equal insulating materials cladding.
In a specific embodiment, the edge of the shaking platform extends downward into the lower surface of the sample bin,
It is contacted to avoid the lower surface of the shaking platform with the sample in sample bin.
It wherein, the part that shaking platform extends downwardly can be different from the material of shaking platform.
Alternatively, in a specific embodiment, the partial region of the lower surface of the sample bin makes described to lower recess
Shaking platform covers the opening of sunk area formation, connects to avoid the sample in the lower surface and sample bin of the shaking platform
Touching.
Wherein, the side wall for forming sunk area can be identical as the material of sample bin, can also be with the material of sample bin not
Together.It is preferable that the material for forming the lower surface of sunk area is transparent material, more preferably glass.It is specific at one
In embodiment, the data collection system includes collector and data analysis module.
In a specific embodiment, the detection analysis instrument further includes lasecon, the lasecon position
In the lower section of the sample bin；The lower surface of the sample bin is transparent.
In a specific embodiment, the detection analysis instrument further includes driving device, and the driving device can be same
When drive the first sample input/output element and the second sample input/output element so that
While sample input in first sample input/output element is to the sample bin, make the sample bin
Interior sample is output in second sample input/output element；Or
While making sample input in second sample input/output element to the sample bin, make the sample
Sample in storehouse is output in first sample input/output element.
In a specific embodiment, first sample input/output element includes first piston and the first liquid storage
Device, the first end of first liquid storage device have the first opening, and the first piston is able to enter described through first opening
The cavity of first liquid storage device, the cavity and the first piston of first liquid storage device are fitted close, first liquid storage device
Second end is connected to the sample bin；
Second sample input/output element includes second piston and the second liquid storage device, and the of second liquid storage device
One end has the second opening, and the second piston is able to enter the cavity of second liquid storage device through second opening, described
The cavity of second liquid storage device and the second piston are fitted close, and the second end of second liquid storage device and the sample bin connect
It is logical；
The driving device is set to the first piston and the exposure being exposed to except the cavity of first liquid storage device
Between the second piston except the cavity of second liquid storage device, to drive the first piston and the second piston
Move back and forth.
In a specific embodiment, the driving device includes gear, and the linkage further includes driving gear
The motor of rotation, and the electrode of the control motor, the gear can drive the first piston and the second piston
Move back and forth, and the direction of first piston movement is contrary with second piston movement；In first storage
The first end of liquid device is equipped with the first gear reverse switch that can change gear rotation direction；The first of second liquid storage device
End is equipped with the second gear reverse switch that can change gear rotation direction；And it is provided on the first piston and first
Gear reverses the first gear of switch cooperation to reverse switch matching piece, is provided in the second piston and reverses with second gear
The second gear of switch cooperation reverses switch matching piece；The electrode reverses switch or second gear to reverse by the first gear
Switch control.
In a specific embodiment, the length of the first piston be the cavity length of first liquid storage device extremely
It is 2 times few；When one end of the first piston reaches the second end of the first liquid storage device, it is exposed to the cavity of first liquid storage device
Except part be the first outer piston；
The length of the second piston is at least 2 times of the cavity length of second liquid storage device；In the second piston
One end reach the second liquid storage device second end when, be exposed to the part except the cavity of second liquid storage device be second outside
Piston.
In a specific embodiment, the outer surface of first outer piston is equipped with the protrusion for increasing frictional force, with
It is matched with the gear；The outer surface of second outer piston be equipped with increase frictional force protrusion, with the gear phase
Cooperation.
In a specific embodiment, outside the contact surface and described second of first outer piston and the gear
The dentalation matched with the gear is all had on piston and the contact surface of the gear.
In a specific embodiment, the dentalation protrudes from the outer surface of first outer piston；With/
Or the dentalation protrudes from the outer surface of second outer piston.
In a specific embodiment, the dentalation is depressed on the outer surface of first outer piston；With/
Or the dentalation is depressed on the outer surface of second outer piston.
In a specific embodiment, described when the first piston and the first gear reverse switch contact
Dentalation is located at the outer end of first liquid storage device；When the second piston and the second gear reverse switch contact,
The dentalation is located at the outer end of second liquid storage device.
The beneficial effect that the application can generate includes:
1) capacity of the shaking platform of the application can change according to experiment demand, i.e., shaking platform meets a large amount of detections
The requirement of cell；And certain triangle vibrating cantalever capacity are very limited.
2) shaking platform of the application is direction vibration, can both be vibrated up and down, can also be with side-to-side vibrations, can be with front and back
Vibration, to reduce the vibration difference of each point on shaking platform, ensure that the accuracy of measurement；And certain three angular oscillations are outstanding
Arm is unilateral vibration, the vibration generated and uneven, therefore, is difficult to reach quasi- using the adhesive capacity of this device detection cell
True degree.
3) in this application, data processing system is directly connect with shaking platform, even if mechanical signal is converted directly into electricity
Signal is learned, there is no the enhanced processing problems of data-signal, it is directly easy not only to obtain data, and avoid what data were amplified
Duplicity；And the detection of certain signals experienced the amplification process of a signal, thus the data obtained are on the one hand not direct enough,
The amplification of another aspect signal is easy to cause data error to become larger.
4) in this application, which is able to carry out real-time quantitative analysis, and meeting processing in time, analysis requires in time, keeps away
Time waste is exempted from；Existing apparatus cannot achieve real-time quantitative analysis.
5) in this application, by filling the connection of parallel operation with laser, this instrument can be expanded for the detection function of material,
New tupe is opened, the requirement of real-time optical treatment is met.Such as it can detecte and controlled with optical dynamic therapy, photo-thermal
Research of the nano particle for the treatment of etc. for cell therapy procedures；Or it can also be used to detection research product using lasecon
Cure mechanism.
6) on the one hand the application driving device realizes the automation of sample input and output operation, on the other hand its knot
Structure is simple, strong operability.Using the resonant vibration platform biological quality sensor-based system of piezoelectric excitation, make to vibrate using oscillator
Platform reaches its resonant frequency, later using sample input/output system perseverance of bi-directional synchronization gear motor control slowly to sample
Input/output sample, need material to be tested or product solution in product storehouse, keep the sample in sample bin to have constant volume to ensure
Amount is recorded the small amplitude variations of shaking platform for a long time, in real time using data collection system, avoided to shaking platform
Influence of noise.In addition, permanent sample capacity also plays the effect for preventing sample spill-over damage instrument.
7) detection analysis instrument for utilizing the application, realizes cell-free label, and injury will not be generated to cell, true to reflect
The bio-toxicity of institute's sample out；Resonant vibration platform sensing has very high sensitivity, and small amplitude variations can also be measured,
Quantitative detection is accurate；For a long time, the variation of Real_time quantitative detection amplitude, rather than take time point type analysis method.
Detailed description of the invention
Fig. 1 shows the workflow schematic diagram of multi-modal dynamic biological toxicity Real_time quantitative detection analyzer.
Fig. 2 shows the instrument and display interface figure corresponding to Fig. 1 general flow chart.
Fig. 3 shows another structural schematic diagram of sample bin Yu shaking platform matching relationship.
Fig. 4 shows the schematic diagram of the linkage of sample input and output.
Fig. 5 shows the schematic diagram of the linkage of another sample input and output.
Fig. 6 shows the reverse switch basic circuit schematic diagram of gear 4.
Component and reference signs list:
1, oscillator；2, shaking platform；3, sample bin；4, gear；5, data collection system；6, data display equipment；7, it moves
State amplitude normalization software interface；8, functional simulation software interface；9, the first sample input/output element；9 ', the second sample is defeated
Enter/output element；10, first piston；10 ', second piston；11, the first liquid storage device；11 ', the second liquid storage device；12,12 ', dentation
Structure；13, first gear reverses switch；13 ', second gear reverses switch；14, first gear reverses switch matching piece；14 ',
Second gear reverses switch matching piece；15, lasecon；16, motor；17, first switch connecting element；18, second switch
Connecting element；19, switch control.
Specific embodiment
The application is described in detail below with reference to embodiment, but the application is not limited to these embodiments.
1 detection analysis instrument of embodiment
As shown in Figure 1, which show multi-modal, dynamic biological toxicity Real_time quantitative detection analyzer workflow letters
Figure.
Wherein, the effect of oscillator 1 is that shaking platform 2 (piezo-electric crystal) is driven by the alternating voltage of application to fix frequency
Rate is vibrated.Oscillator 1 and shaking platform 2, using depth positive feedback cross value, are closed back in a manner of Multi-contact by corner
Road controls driving frequency, to meet the stress vibration mode of low error oscillator.Oscillator 1 drives shaking platform 2 to reach resonance frequency
Rate, amplitude of the shaking platform 2 for a long time, during real-time testing down to V grades of 1 μ can also be acquired simultaneously by data collection system 5
Data processing is carried out by processing software (such as dynamic amplitude normalization software and functional simulation software).
Shaking platform 2: it is driven by 1 driving frequency of oscillator, is vibrated under fixed frequency.Cell or biological tissue
When its surface adhesion or poisoning fall off, the external pressure for acting on surface will cause the bending change of oscillator to make amplitude produce
Raw corresponding polarization.
Collector (a part of data collection system 5): amplitude polarization signal is acquired in real time, is converted into filtering base
Line, and signal resolution meets 24bit or requirements above.
Data analysis module (a part of data collection system 5): carry out for a long time, real-time raw data acquisition
Meanwhile the filtering baseline from collector is normalized, and cell detachment is obtained by calculation or biological tissue is different
Amplitude variations (i.e. progress dynamic amplitude normalized Analysis) after change, then by exponential function (see the functional simulation software of Fig. 2
Interface 8) sunykatuib analysis its degradation factor, to achieve the purpose that carry out quantitative analysis to characteristics such as bio-toxicities.Wherein, data
Acquisition system 5 first uses dynamic amplitude normalization software and functional simulation software.Wherein, the function of dynamic amplitude normalization software
Can eliminate magnitude origin line drift, steady baseline, i.e. baseline correction and elimination offset；The function of functional simulation software: later period
When data are analyzed, the amplitude variations amount provided in certain period can be calculated according to demand.Dynamic amplitude normalizes software
It can be obtained by the ordinary skill in the art with functional simulation software.
The foundation equation of amplitude normalization uses higher order polynomial, and f (t) is immediate movement function, and y is the position of equilbrium position
It moves:
The derivative of above-mentioned multinomial sum is 0, does normalized to its amplitude balance point, shown in following formula:
anan-1...a1a0
For functional simulation program according to exponential function equation, A is the amplitude of shaking platform 2, A0For the maximum vibration of shaking platform 2
Width, B are that the amplitude of shaking platform 2 passs add drop coefficient, and t is the time of vibration of shaking platform 2, acquire B coefficient detailed process such as
Under:
A (t)=A0e-Bt
LnA (t)=lnA0-Bt
Sample bin 3: being internally provided with shaking platform 2, and side wall has the vertically and horizontally liquid for connecting a set of motor precision control
Input/output element 9,9 ' (see Fig. 4), for example, can control input/output element 9,9 ' arrives 10 influenced on oscillator noiseless
The two-way flow velocity of μ L/min.By this system, can into sample bin 3 input/output specimen material.This set system can control
It is consistent to pass in and out flow velocity, makes to reach dynamic equilibrium in sample bin 3, keeps the constant volume of the fluid in sample bin 3 constant, and flow velocity
It is small, to keep shaking platform 2 in stable condition, avoid the influence of noise generated due to the variation of sample size to shaking platform 2.
In addition, this sample bin 3 is required due to meet observation living cells toxicity variation for a long time, so the biotic environment kept constant
It is the necessary condition of its detection.For example, 37 DEG C of constant temperature can be heated and kept, it is passed through 5%CO2Carbon dioxide is raw to reach cell
The environmental condition deposited.
Lasecon 15: its lower section for being located at sample bin 3, different wave length exciting light needed for meeting different materials generate
Light-initiated biochemical reaction, to make tested organism that corresponding change occur.It can be used for product photo-thermal/optical dynamic therapy
Deng research.The data measured are finally shown on display screen by high-resolution data collection system.
As shown in Figure 2, it is shown that instrument and display interface figure corresponding to Fig. 1 general flow chart.It includes sample input/defeated
Element 9 out, 9 ' (see Fig. 4), sample bin 3, shaking platform 2, oscillator 1, data collection system 5 and data display equipment 6；Wherein,
Sample input/output element 9,9 ' is connected to the sample bin 3；The shaking platform 2 is located in the sample bin 3；The vibration
It swings device 2 to be located at outside the sample bin 3, and the shaking platform 2 is connect with the oscillator 3；The data collection system 5
In outside the sample bin 3, and it is connect with the shaking platform 2；The data display equipment 6 is connect with the data collection system 5.
Specifically, the edge of shaking platform 2 extends downward into the lower surface of sample bin 3, to avoid the following table of shaking platform 2
Face is contacted with the sample in sample bin 3.
It wherein, the part that shaking platform 2 extends downwardly can be different from the material of shaking platform 2.
Alternatively, making to vibrate as shown in figure 3, the partial region of the lower surface of sample bin 3, which is recessed downwards, forms sunk area 31
Platform 2 covers the opening of the sunk area 31, contacts to avoid the lower surface of shaking platform 2 with the sample in sample bin 3.
Wherein, the side wall 32 for forming sunk area 31 can be identical as the material of sample bin, can also be with the material of sample bin
Matter is different.It is preferable that the material for forming the lower surface 33 of sunk area 31 is transparent material, more preferably glass.
In addition, the edge of shaking platform 2 is fixedly connected with elastic element 34, elastic element 34 is connect with external voltage.
As shown in figure 4, mainly showing the schematic diagram of the linkage of sample input and output.The sample input and output
Linkage include the first sample input/output element 9, the second sample input/output element 9 ', sample bin 3 and driving dress
It sets.
First sample input/output element 9 includes first piston 10 and the first liquid storage device 11, first liquid storage device 11
First end has the first opening, and the first piston 10 is able to enter the chamber of first liquid storage device 11 through first opening
Body, the cavity of first liquid storage device 11 and the first piston 10 are fitted close, the second end of first liquid storage device 11 with
The sample bin 3 is connected to；
Second sample input/output element 9 ' includes second piston 10 ' and the second liquid storage device 11 ', second storage
The first end of liquid device 11 ' has the second opening, and the second piston 10 ' is able to enter second liquid storage through second opening
The cavity of device 11 ', the cavity of second liquid storage device 11 ' and the second piston 10 ' are fitted close, second liquid storage device
11 ' second end is connected to the sample bin 3；
The driving device is set between the first piston 10 and the second piston 10 ', to drive described
One piston 10 and the second piston 10 ' move back and forth.
The driving device includes gear 4, and linkage further includes the motor of sliding tooth wheel rotation, and the control horse
The electrode reached, gear 4 can drive first piston 10 and second piston 10 ' to move back and forth, and the side that first piston 10 is mobile
It is contrary to being moved with second piston 10 '；4 rotation direction of gear can be changed by being equipped in the first end of the first liquid storage device 11
First gear reverse switch 13；The of 4 rotation direction of gear can be changed by being equipped in the first end of second liquid storage device 11 '
Two gears reverse switch 13 '；And the first gear for reversing switch 13 to cooperate with first gear is provided on first piston 10
Switch matching piece 14 is reversed, the second gear for reversing switch 13 ' to cooperate with second gear is provided in the second piston 10 '
Reverse switch matching piece 14 '；The electrode reverses switch 13 or second gear that switch 13 ' is reversed to control by the first gear.
Specifically, such as Fig. 5, first gear reverses switch 13 to be arranged in the first opening, and protrudes from the first liquid storage device 11
On shell；Second gear reverses switch 13 ' to be arranged in the second opening, and protrudes from 11 ' shell of the second liquid storage device.In addition,
It is the protrusion for protruding from first piston 10 that first gear, which reverses switch matching piece 14, is generally located on the middle part of first piston 10,
Or the place close to middle part；It is the protrusion for protruding from second piston 10 ' that second gear, which reverses switch matching piece 14 ', general to be arranged
At the middle part of second piston 10 ', or close to the place at middle part.It is moved through in first piston 10 to the second end of the first liquid storage device 11
Cheng Zhong, first gear reverses switch matching piece 14 that can move closer to first gear and reverses switch 13, until reversing with first gear
Switch 13 contacts, and triggers gear at this time and reverses.Or in second piston 10 ' to the second end motion process of the second liquid storage device 11 '
In, second gear reverses switch matching piece 14 ' that can move closer to second gear and reverses switch 13 ', until reversing with second gear
Switch 13 ' contacts, and triggers gear at this time and reverses.And so on.
It is all had and gear 4 on the contact surface and second piston 10 ' of first piston 10 and gear 4 and the contact surface of gear 4
The dentalation 12,12 ' matched；
Dentalation 12 protrudes from the surface of first piston 10；And/or dentalation 12 ' protrudes from second piston 10 '
Surface on.The length that especially can be designed as first piston 10 is at least 2 times of cavity length of the first liquid storage device 11；?
When one end of first piston 10 reaches the second end of the first liquid storage device 11, it is exposed to the part except the cavity of the first liquid storage device 11
It is the first internal piston (with color depth in figure into the part within the cavity of the first liquid storage device 11 for the first outer piston
It is shallowly distinguished with the first outer piston)；At this point, dentalation 12 protrudes from the surface of the first outer piston.Second piston 10 '
Length is at least 2 times of the cavity length of the second liquid storage device 11 '；The second liquid storage device 11 ' is reached in one end of second piston 10 '
When second end, the part being exposed to except the cavity of the second liquid storage device 11 ' is the second outer piston, into the second liquid storage device 11 '
Cavity within part be the second internal piston (in figure with shade and the second outer piston differentiation)；At this point, dentation
Structure 12 ' protrudes from the surface of the second outer piston.
In addition, dentalation 12 can also be depressed on the surface of first piston 10；It is living that dentalation 12 ' is depressed in second
On the surface of plug 10 '.Especially can be designed as first piston 10 length be the first liquid storage device 11 cavity length at least 2
Times；When one end of first piston 10 reaches the second end of the first liquid storage device 11, it is exposed to except the cavity of the first liquid storage device 11
Part be the first outer piston, into the part within the cavity of the first liquid storage device 11 be the first internal piston (in figure with
Shade and the first outer piston are distinguished)；At this point, dentalation 12 can also be depressed on the surface of the first outer piston.
The length of second piston 10 ' is at least 2 times of the cavity length of the second liquid storage device 11 '；The is reached in one end of second piston 10 '
When the second end of two liquid storage devices 11 ', being exposed to the part except the cavity of the second liquid storage device 11 ' is the second outer piston, is entered
Part within the cavity of second liquid storage device 11 ' is the second internal piston (with shade and the second outer piston area in figure
Point)；At this point, dentalation 12 ' can also be depressed on the surface of the second outer piston.
First gear reverses switch matching piece 14 also to can be set on the first internal piston, and at this point, first gear
Switch matching piece 14 is reversed to be positioned proximate to the position of the first outer piston；Second gear reverses switch matching piece 14 ' that can also set
It sets on the second internal piston, and at this point, second gear, which reverses, switchs the position that matching piece 14 ' is positioned proximate to the second outer piston
It sets.
Preferably, first gear, which reverses, switchs the handover that the first outer piston and the first internal piston is arranged in matching piece 14
Place；Second gear, which reverses, switchs the junction that the second outer piston and the second internal piston is arranged in matching piece 14 '.
As shown in fig. 6, the reverse for gear 4 switchs basic circuit schematic diagram.Wherein 16 be motor, when first gear reverses
When switch 13 and first gear reverse switch matching piece 14 to contact, switch control 19 is bounced off out first switch connecting element
17, and contacted with second switch connecting element 18；When second gear reverses switch 13 ' and second gear to reverse switch matching piece
When 14 ' contact, switch control 19 is bounced off out second switch connecting element 18, and is contacted with first switch connecting element 17.
This dynamic biological toxicity Real_time quantitative detection analyzer can acquire at least 24 hours initial data, and adopt
The high resolution of collection, amplitude wave deformationization are subtle as it can be seen that reach the real-time visible and easy quantitative inspection of organism slight change
?.In addition, multi-modal laser is cooperated to meet the requirement of multi-mode organism stress reaction, the bio-toxicity for detecting detected materials becomes
Change process, to help to analyze the toxicity type and mechanism of action of the material, this provides organism toxicologic study
Effective experiment is supported, and provides completely new detection platform to the research and development of newtype drug.
Embodiment 2 is applied
The preparation of nanoparticle
According to the method that document provides, (2017,15 (1): Journal of Nanobiotechnology 23)), uses lemon
Lemon acid sodium reduction synthesizes common nano Au particle in present nanosecond medical science, the specific steps are as follows: in three-necked flask plus
Enter 144ml ultrapure water, be heated to boiling, the citric acid (60mM) for adding 3.5ml sodium citrate (60mM) and 1.5ml acutely stirs
It mixes.100 microlitres of EDTA is added, adds 1ml gold chloride (25mM).When the color of mixture becomes claret, closes and add
Heat when falling to a certain temperature, is dipped in ice water and stops reaction.Synthesize the ball shaped nano gold particle that partial size is 13nm.
Later by polyethylene glycol being coated in nanometer gold surface, to improve the biology of this nanoparticle after ligand exchange
Compatibility and stability.
Hela cell is tested to the maximal oxygen taken amount of nanoparticle
According to document provide method (Journal of Nanobiotechnology, 2017,15 (1): 23), this experiment
Herein cover dynamic biological toxicity Real_time quantitative detection analyzer on carry out, by certain density Hela cell by sample input/
Environment is maintained 37 DEG C with the slow constant speed of speed of 10 μ l/min in input/output sample bin by output element, 5%CO2
Controlled condition under, when observed amplitude increases to stationary value, by the variation of amplitude in data display equipment 6, obtain and be adhered to vibration
Number of cells on moving platform.
Later, the slow constant speed of certain density nano Au particle is injected in sample bin 3, the rising of Observable amplitude reaches
Certain altitude can stablize a period of time, then since exponential decay can be presented in cytotoxic amplitude.It can be calculated by calculating
Maximal oxygen taken amount of the Hela cell to gold nanoparticle.
Monitor the optical dynamic therapy process of up-conversion nanoparticles
Nano Au particle is changed into NaGdF4:Yb/Tm@TiO2Upper conversion particles, wherein TiO2Make photosensitizer.When cancer is thin
After born of the same parents absorb up-conversion nanoparticles, multi-modal lasecon is transformed into 980nm, irradiates shaking platform, there is light
The nanoparticle of dynamic therapy effect can discharge active oxygen and kill cancer cell under the irradiation of laser.This process reaction is being shaken
In the variation of width, can further it analyze whereby.
The above is only several embodiments of the application, not does any type of limitation to the application, although this Shen
Please disclosed as above with preferred embodiment, however not to limit the application, any person skilled in the art is not taking off
In the range of technical scheme, a little variation or modification are made using the technology contents of the disclosure above and is equal to
Case study on implementation is imitated, is belonged in technical proposal scope.
Claims (10)
1. a kind of detection analysis instrument comprising the first sample input/output element, the second sample input/output element, sample
Storehouse, shaking platform, oscillator, data collection system and data display equipment；Wherein, first sample input/output element and
Second sample input/output element is connected to the sample bin respectively；The shaking platform is located in the sample bin；Institute
It states oscillator to be located at outside the sample bin, and the shaking platform is connect with the oscillator；The data collection system position
In outside the sample bin, and it is connect with the shaking platform；The data display equipment is connect with the data collection system.
2. detection analysis instrument according to claim 1, which is characterized in that the shaking platform is by pressure sensitive or vibration stone
English material is constituted.
3. detection analysis instrument according to claim 1, which is characterized in that the edge and elastic element of the shaking platform are solid
Fixed connection, the elastic element are connect with external voltage.
4. detection analysis instrument according to claim 1, which is characterized in that the data collection system includes collector sum number
According to analysis module.
5. detection analysis instrument according to claim 1, which is characterized in that the detection analysis instrument further includes laser conversion
Device, the lasecon are located at the lower section of the sample bin；The lower surface of the sample bin is transparent.
6. detection analysis instrument according to claim 1, which is characterized in that the detection analysis instrument further includes driving device,
The driving device can drive the first sample input/output element and the second sample input/output element simultaneously, so that
While sample input in first sample input/output element is to the sample bin, make in the sample bin
Sample is output in second sample input/output element；Or
While making sample input in second sample input/output element to the sample bin, make in the sample bin
Sample be output in first sample input/output element.
7. detection analysis instrument according to claim 6, which is characterized in that first sample input/output element includes
First piston and the first liquid storage device, the first end of first liquid storage device have the first opening, and the first piston is through described the
One opening is able to enter the cavity of first liquid storage device, and cavity and the first piston of first liquid storage device are closely matched
It closes, the second end of first liquid storage device is connected to the sample bin；
Second sample input/output element includes second piston and the second liquid storage device, the first end of second liquid storage device
With the second opening, the second piston is open through described second is able to enter the cavity of second liquid storage device, and described second
The cavity of liquid storage device and the second piston are fitted close, and the second end of second liquid storage device is connected to the sample bin；
The driving device is set to the first piston being exposed to except the cavity of first liquid storage device and is exposed to institute
It states between the second piston except the cavity of the second liquid storage device, to drive the first piston and the second piston back and forth
It is mobile.
8. detection analysis instrument according to claim 7, which is characterized in that the driving device includes gear, the linkage
Device further includes the motor of sliding tooth wheel rotation, and the electrode of the control motor, the gear can drive described first
Piston and the second piston move back and forth, and the direction and the direction of second piston movement that the first piston is mobile
On the contrary；The first gear reverse switch that can change gear rotation direction is equipped in the first end of first liquid storage device；Institute
The first end for stating the second liquid storage device is equipped with the second gear reverse switch that can change gear rotation direction；And described first
It is provided on piston and reverses the first gear of switch cooperation to reverse switch matching piece with first gear, set in the second piston
It is equipped with and reverses the second gear of switch cooperation to reverse switch matching piece with second gear；The electrode is reversed by the first gear
Switch or second gear reverse switch control.
9. detection analysis instrument according to claim 8, which is characterized in that the length of the first piston is first storage
At least 2 times of the cavity length of liquid device；When one end of the first piston reaches the second end of the first liquid storage device, it is exposed to institute
Stating the part except the cavity of the first liquid storage device is the first outer piston；
The length of the second piston is at least 2 times of the cavity length of second liquid storage device；The one of the second piston
When end reaches the second end of the second liquid storage device, being exposed to the part except the cavity of second liquid storage device is that the second outside is living
Plug.
10. detection analysis instrument according to claim 9, which is characterized in that the outer surface of first outer piston is equipped with
Increase the protrusion of frictional force, to match with the gear；The outer surface of second outer piston, which is equipped with, increases frictional force
Protrusion, to be matched with the gear；Or
On the contact surface and second outer piston of first outer piston and the gear and the contact surface of the gear
All have the dentalation matched with the gear；
It is preferred that the dentalation protrudes from the outer surface of first outer piston；And/or the dentalation protrudes from
On the outer surface of second outer piston；Or
It is preferred that the dentalation is depressed on the outer surface of first outer piston；And/or the dentalation is depressed in
On the outer surface of second outer piston.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710508203.5A CN109142657B (en) | 2017-06-28 | 2017-06-28 | Detection analyzer |
| EP18822637.7A EP3591394B1 (en) | 2017-06-28 | 2018-01-09 | Detection analyzer |
| US16/486,587 US11333661B2 (en) | 2017-06-28 | 2018-01-09 | Detection analyzer |
| PCT/CN2018/071835 WO2019000902A1 (en) | 2017-06-28 | 2018-01-09 | Detection analyzer |
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| CN201710508203.5A CN109142657B (en) | 2017-06-28 | 2017-06-28 | Detection analyzer |
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| CN109142657B CN109142657B (en) | 2020-08-07 |
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| CN109142657B (en) | 2020-08-07 |
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Address after: No. 99 Xuelin Road, Ningbo City, Zhejiang Province, 315300 Patentee after: Ningbo Cixi Institute of Biomedical Engineering Address before: 315300 No.145, Danshan North Road, Cixi City, Ningbo City, Zhejiang Province Patentee before: CIXI INSTITUTE OF BIOMEDICAL ENGINEERING, NINGBO INSTITUTE OF INDUSTRIAL TECHNOLOGY, CHINESE ACADEMY OF SCIENCES |